PLoS Genetics最新文献

{"title":"Rapid changes in plasma corticosterone and medial amygdala transcriptome profiles during social status change reveal molecular pathways associated with a major life history transition in mouse dominance hierarchies.","authors":"Tyler M Milewski, Won Lee, Rebecca L Young, Hans A Hofmann, James P Curley","doi":"10.1371/journal.pgen.1011548","DOIUrl":"10.1371/journal.pgen.1011548","url":null,"abstract":"<p><p>Social hierarchies are a common form of social organization across species. Although hierarchies are largely stable across time, animals may socially ascend or descend within hierarchies depending on environmental and social challenges. Here, we develop a novel paradigm to study social ascent and descent within male CD-1 mouse social hierarchies. We show that mice of all social ranks rapidly establish new stable social hierarchies when placed in novel social groups with animals of equivalent social status. Seventy minutes following social hierarchy formation, males that were socially dominant prior to being placed into new social hierarchies exhibit higher increases in plasma corticosterone and vastly greater transcriptional changes in the medial amygdala (MeA), which is central to the regulation of social behavior, compared to males who were socially subordinate prior to being placed into a new hierarchy. Specifically, the loss of social status in a new hierarchy (social descent) is associated with reductions in MeA expression of myelination and oligodendrocyte differentiation genes. Maintaining high social status is associated with high expression of genes related to cholinergic signaling in the MeA. Conversely, gaining social status in a new hierarchy (social ascent) is related to relatively few unique rapid changes in the MeA. We also identify novel genes associated with social transition that show common changes in expression when animals undergo either social descent or social ascent compared to maintaining their status. Two genes, Myosin binding protein C1 (Mybpc1) and μ-Crystallin (Crym), associated with vasoactive intestinal polypeptide (VIP) and thyroid hormone pathways respectively, are highly upregulated in socially transitioning individuals. Further, increases in genes associated with synaptic plasticity, excitatory glutamatergic signaling and learning and memory pathways were observed in transitioning animals suggesting that these processes may support rapid social status changes.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 1","pages":"e1011548"},"PeriodicalIF":4.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The piRNA protein Asz1 is essential for germ cell and gonad development in zebrafish and exhibits differential necessities in distinct types of germ granules.","authors":"Adam Ahmad, Yoel Bogoch, Gal Shvaizer, Noga Guler, Karine Levy, Yaniv M Elkouby","doi":"10.1371/journal.pgen.1010868","DOIUrl":"10.1371/journal.pgen.1010868","url":null,"abstract":"<p><p>Germ cells are essential for fertility, embryogenesis, and reproduction. Germline development requires distinct types of germ granules, which contains RNA-protein (RNP) complexes, including germ plasm in embryos, piRNA granules in gonadal germ cells, and the Balbiani body (Bb) in oocytes. However, the regulation of RNP assemblies in zebrafish germline development are still poorly understood. Asz1 is a piRNA protein in Drosophila and mice. Zebrafish Asz1 localizes to both piRNA and Bb granules, with yet unknown functions. Here, we hypothesized that Asz1 functions in germ granules and germline development in zebrafish. We generated asz1 mutant fish to determine the roles of Asz1 in germ cell development. We show that Asz1 is dispensable for somatic development, but essential for germ cell and gonad development. asz1-/- fish developed exclusively as sterile males with severely underdeveloped testes that lacked germ cells. In asz1 mutant juvenile gonads, germ cells undergo extensive apoptosis, demonstrating that Asz1 is essential for germ cell survival. Mechanistically, we provide evidence to conclude that zygotic Asz1 is not required for primordial germ cell specification or migration to the gonad, but is essential during post-embryonic gonad development, likely by suppressing the expression of germline transposons. Increased transposon expression and mis-organized piRNA granules in asz1 mutants, argue that zebrafish Asz1 functions in the piRNA pathway. We generated asz1;tp53 fish to partially rescue ovarian development, revealing that Asz1 is also essential for oogenesis. We further showed that in contrast with piRNA granules, Asz1 is dispensable for Bb granule formation, as shown by normal Bb localization of Buc and dazl. By uncovering Asz1 as an essential regulator of germ cell survival and gonadogenesis in zebrafish, and determining its differential necessity in distinct germ granule types, our work advances our understanding of the developmental genetics of reproduction and fertility, as well as of germ granule biology.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 1","pages":"e1010868"},"PeriodicalIF":4.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversification and recurrent adaptation of the synaptonemal complex in Drosophila.","authors":"Rana Zakerzade, Ching-Ho Chang, Kamalakar Chatla, Ananya Krishnapura, Samuel P Appiah, Jacki Zhang, Robert L Unckless, Justin P Blumenstiel, Doris Bachtrog, Kevin H-C Wei","doi":"10.1371/journal.pgen.1011549","DOIUrl":"10.1371/journal.pgen.1011549","url":null,"abstract":"<p><p>The synaptonemal complex (SC) is a protein-rich structure essential for meiotic recombination and faithful chromosome segregation. Acting like a zipper to paired homologous chromosomes during early prophase I, the complex is a symmetrical structure where central elements are connected on two sides by the transverse filaments to the chromatin-anchoring lateral elements. Despite being found in most major eukaryotic taxa implying a deeply conserved evolutionary origin, several components of the complex exhibit unusually high rates of sequence turnover. This is puzzlingly exemplified by the SC of Drosophila, where the central elements and transverse filaments display no identifiable homologs outside of the genus. Here, we exhaustively examine the evolutionary history of the SC in Drosophila taking a comparative phylogenomic approach with high species density to circumvent obscured homology due to rapid sequence evolution. Contrasting starkly against other genes involved in meiotic chromosome pairing, SC genes show significantly elevated rates of coding evolution due to a combination of relaxed constraint and recurrent, widespread positive selection. In particular, the central element cona and transverse filament c(3)G have diversified through tandem and retro-duplications, repeatedly generating paralogs with novel germline activity. In a striking case of molecular convergence, c(3)G paralogs that independently arose in distant lineages evolved under positive selection to have convergent truncations to the protein termini and elevated testes expression. Surprisingly, the expression of SC genes in the germline is prone to change suggesting recurrent regulatory evolution which, in many species, resulted in high testes expression even though Drosophila males are achiasmic. Overall, our study recapitulates the poor conservation of SC components, and further uncovers that the lack of conservation extends to other modalities including copy number, genomic locale, and germline regulation. Considering the elevated testes expression in many Drosophila species and the common ancestor, we suggest that the activity of SC genes in the male germline, while still poorly understood, may be a prime target of constant evolutionary pressures driving repeated adaptations and innovations.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 1","pages":"e1011549"},"PeriodicalIF":4.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel genes responsible for a pollen killer present in local natural populations of Arabidopsis thaliana.","authors":"Anthony Ricou, Matthieu Simon, Rémi Duflos, Marianne Azzopardi, Fabrice Roux, Françoise Budar, Christine Camilleri","doi":"10.1371/journal.pgen.1011451","DOIUrl":"10.1371/journal.pgen.1011451","url":null,"abstract":"<p><p>Gamete killers are genetic loci that distort segregation in the progeny of hybrids because the killer allele promotes the elimination of the gametes that carry the sensitive allele. They are widely distributed in eukaryotes and are important for understanding genome evolution and speciation. We had previously identified a pollen killer in hybrids between two distant natural accessions of Arabidopsis thaliana. This pollen killer involves three genetically linked genes, and we previously reported the identification of the gene encoding the antidote that protects pollen grains from the killer activity. In this study, we identified the two other genes of the pollen killer by using CRISPR-Cas9 induced mutants. These two genes are necessary for the killer activity that we demonstrated to be specific to pollen. The cellular localization of the pollen killer encoded proteins suggests that the pollen killer activity involves the mitochondria. Sequence analyses reveal predicted domains from the same families in the killer proteins. In addition, the C-terminal half of one of the killer proteins is identical to the antidote, and one amino acid, crucial for the antidote activity, is also essential for the killer function. Investigating more than 700 worldwide accessions of A. thaliana, we confirmed that the locus is subject to important structural rearrangements and copy number variation. By exploiting available de novo genomic sequences, we propose a scenario for the emergence of this pollen killer in A. thaliana. Furthermore, we report the co-occurrence and behavior of killer and sensitive genotypes in several local populations, a prerequisite for studying gamete killer evolution in the wild. This highlights the potential of the Arabidopsis model not only for functional studies of gamete killers but also for investigating their evolutionary trajectories at complementary geographical scales.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 1","pages":"e1011451"},"PeriodicalIF":4.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The dependence of shugoshin on Bub1-kinase activity is dispensable for the maintenance of spindle assembly checkpoint response in Cryptococcus neoformans.","authors":"Satya Dev Polisetty, Krishna Bhat, Kuladeep Das, Ivan Clark, Kevin G Hardwick, Kaustuv Sanyal","doi":"10.1371/journal.pgen.1011552","DOIUrl":"10.1371/journal.pgen.1011552","url":null,"abstract":"<p><p>During chromosome segregation, the spindle assembly checkpoint (SAC) detects errors in kinetochore-microtubule attachments. Timely activation and maintenance of the SAC until defects are corrected is essential for genome stability. Here, we show that shugoshin (Sgo1), a conserved tension-sensing protein, ensures the maintenance of SAC signals in response to unattached kinetochores during mitosis in a basidiomycete budding yeast Cryptococcus neoformans. Sgo1 maintains optimum levels of Aurora B kinase Ipl1 and protein phosphatase 1 (PP1) at kinetochores. The absence of Sgo1 results in the loss of Aurora BIpl1 with a concomitant increase in PP1 levels at kinetochores. This leads to a premature reduction in the kinetochore-bound Bub1 levels and early termination of the SAC signals. Intriguingly, the kinase function of Bub1 is dispensable for shugoshin's subcellular localization. Sgo1 is predominantly localized to spindle pole bodies (SPBs) and along the mitotic spindle with a minor pool at kinetochores. In the absence of proper kinetochore-microtubule attachments, Sgo1 reinforces the Aurora B kinaseIpl1-PP1 phosphatase balance, which is critical for prolonged maintenance of the SAC response.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 1","pages":"e1011552"},"PeriodicalIF":4.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ambivalent partnership of the Drosophila posterior class Hox protein Abdominal-B with Extradenticle and Homothorax.","authors":"Jesús R Curt, Paloma Martín, David Foronda, Bruno Hudry, Ramakrishnan Kannan, Srividya Shetty, Samir Merabet, Andrew J Saurin, Yacine Graba, Ernesto Sánchez-Herrero","doi":"10.1371/journal.pgen.1011355","DOIUrl":"10.1371/journal.pgen.1011355","url":null,"abstract":"<p><p>Hox proteins, a sub-group of the homeodomain (HD) transcription factor family, provide positional information for axial patterning in development and evolution. Hox protein functional specificity is reached, at least in part, through interactions with Pbc (Extradenticle (Exd) in Drosophila) and Meis/Prep (Homothorax (Hth) in Drosophila) proteins. Most of our current knowledge of Hox protein specificity stems from the study of anterior and central Hox proteins, identifying the molecular and structural bases for Hox/Pbc/Meis-Prep cooperative action. Posterior Hox class proteins, Abdominal-B (Abd-B) in Drosophila and Hox9-13 in vertebrates, have been comparatively less studied. They strongly diverge from anterior and central class Hox proteins, with a low degree of HD sequence conservation and the absence of a core canonical Pbc interaction motif. Here we explore how Abd-B function interface with that of Exd/Hth using several developmental contexts, studying mutual expression control, functional dependency and intrinsic protein requirements. Results identify cross-regulatory interactions setting relative expression and activity levels required for proper development. They also reveal organ-specific requirement and a binary functional interplay with Exd and Hth, either antagonistic, as previously reported, or synergistic. This highlights context specific use of Exd/Hth, and a similar context specific use of Abd-B intrinsic protein requirements.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 1","pages":"e1011355"},"PeriodicalIF":4.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"metaGE: Investigating genotype x environment interactions through GWAS meta-analysis.","authors":"Annaïg De Walsche, Alexis Vergne, Renaud Rincent, Fabrice Roux, Stéphane Nicolas, Claude Welcker, Sofiane Mezmouk, Alain Charcosset, Tristan Mary-Huard","doi":"10.1371/journal.pgen.1011553","DOIUrl":"10.1371/journal.pgen.1011553","url":null,"abstract":"<p><p>Elucidating the genetic components of plant genotype-by-environment interactions is of key importance in the context of increasing climatic instability, diversification of agricultural practices and pest pressure due to phytosanitary treatment limitations. The genotypic response to environmental stresses can be investigated through multi-environment trials (METs). However, genome-wide association studies (GWAS) of MET data are significantly more complex than that of single environments. In this context, we introduce metaGE, a flexible and computationally efficient meta-analysis approach for jointly analyzing single-environment GWAS of any MET experiment. The metaGE procedure accounts for the heterogeneity of quantitative trait loci (QTL) effects across the environmental conditions and allows the detection of QTL whose allelic effect variations are strongly correlated to environmental cofactors. We evaluated the performance of the proposed methodology and compared it to two competing procedures through simulations. We also applied metaGE to two emblematic examples: the detection of flowering QTLs whose effects are modulated by competition in Arabidopsis and the detection of yield QTLs impacted by drought stresses in maize. The procedure identified known and new QTLs, providing valuable insights into the genetic architecture of complex traits and QTL effects dependent on environmental stress conditions. The whole statistical approach is available as an R package.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 1","pages":"e1011553"},"PeriodicalIF":4.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADELLE: A global testing method for trans-eQTL mapping.","authors":"Takintayo Akinbiyi, Mary Sara McPeek, Mark Abney","doi":"10.1371/journal.pgen.1011563","DOIUrl":"10.1371/journal.pgen.1011563","url":null,"abstract":"<p><p>Understanding the genetic regulatory mechanisms of gene expression is an ongoing challenge. Genetic variants that are associated with expression levels are readily identified when they are proximal to the gene (i.e., cis-eQTLs), but SNPs distant from the gene whose expression levels they are associated with (i.e., trans-eQTLs) have been much more difficult to discover, even though they account for a majority of the heritability in gene expression levels. A major impediment to the identification of more trans-eQTLs is the lack of statistical methods that are powerful enough to overcome the obstacles of small effect sizes and large multiple testing burden of trans-eQTL mapping. Here, we propose ADELLE, a powerful statistical testing framework that requires only summary statistics and is designed to be most sensitive to SNPs that are associated with multiple gene expression levels, a characteristic of many trans-eQTLs. In simulations, we show that for detecting SNPs that are associated with 0.1%-2% of 10,000 traits, among the 8 methods we consider ADELLE is clearly the most powerful overall, with either the highest power or power not significantly different from the highest for all settings in that range. We apply ADELLE to a mouse advanced intercross line data set and show its ability to find trans-eQTLs that were not significant under a standard analysis. We also apply ADELLE to trans-eQTL mapping in the eQTLGen data, and for 1,451 previously identified trans-eQTLs, we discover trans association with additional expression traits beyond those previously identified. This demonstrates that ADELLE is a powerful tool at uncovering trans regulators of genetic expression.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 1","pages":"e1011563"},"PeriodicalIF":4.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic gradual reduction of OGT activity unveils the essential role of O-GlcNAc in the mouse embryo.","authors":"Sara Formichetti, Agnieszka Sadowska, Michela Ascolani, Julia Hansen, Kerstin Ganter, Christophe Lancrin, Neil Humphreys, Mathieu Boulard","doi":"10.1371/journal.pgen.1011507","DOIUrl":"10.1371/journal.pgen.1011507","url":null,"abstract":"<p><p>The reversible glycosylation of nuclear and cytoplasmic proteins (O-GlcNAcylation) is catalyzed by a single enzyme, namely O-GlcNAc transferase (OGT). The mammalian Ogt gene is X-linked, and it is essential for embryonic development and for the viability of proliferating cells. We perturbed OGT's function in vivo by creating a murine allelic series of four single amino acid substitutions, reducing OGT's catalytic activity to a range of degrees. The severity of the embryonic lethality was proportional to the extent of impairment of OGT's catalysis, demonstrating that the O-GlcNAc modification itself is required for early development. We identified hypomorphic Ogt alleles that perturb O-GlcNAc homeostasis while being compatible with embryogenesis. The analysis of the transcriptomes of the mutant embryos at different developmental stages suggested a sexually-dimorphic developmental delay caused by the decrease in O-GlcNAc. Furthermore, a mild reduction of OGT's enzymatic activity was sufficient to loosen the silencing of endogenous retroviruses in vivo.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 1","pages":"e1011507"},"PeriodicalIF":4.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining fine-mapping: Effect sizes and regional heritability.","authors":"Christian Benner, Anubha Mahajan, Matti Pirinen","doi":"10.1371/journal.pgen.1011480","DOIUrl":"10.1371/journal.pgen.1011480","url":null,"abstract":"<p><p>Recent statistical approaches have shown that the set of all available genetic variants explains considerably more phenotypic variance of complex traits and diseases than the individual variants that are robustly associated with these phenotypes. However, rapidly increasing sample sizes constantly improve detection and prioritization of individual variants driving the associations between genomic regions and phenotypes. Therefore, it is useful to routinely estimate how much phenotypic variance the detected variants explain for each region by taking into account the correlation structure of variants and the uncertainty in their causal status. Here we extend the FINEMAP software to estimate the effect sizes and regional heritability under the probabilistic model that assumes a handful of causal variants per region. Using the UK Biobank (UKB) data to simulate genomic regions, we demonstrate that FINEMAP provides higher precision and enables more detailed decomposition of regional heritability into individual variants than the variance component model implemented in BOLT or the fixed-effect model implemented in HESS, particularly when there are only a few causal variants in the fine-mapped region. Using data from 2,940 plasma proteins from the UKB study, we observed that on average FINEMAP identified 2.5 causal variants at an association signal and captured 36% more regional heritability than the variant with the lowest P-value. We estimate that in genomic regions with notable contribution to the total heritability, FINEMAP captures on average 13% and 40% more heritability than BOLT and HESS respectively. Our analysis shows how FINEMAP, BOLT and HESS relate to each other in cases where inference of a variant-level picture of the regional genetic architecture is possible.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 1","pages":"e1011480"},"PeriodicalIF":4.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}